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We established an experimental co-culture system for renal tubular cells and adipocytes to investigate kidney stone formation mechanisms under metabolic syndrome (MetS) conditions and examined the interaction between these cells morphologically and genetically. M-1s and 3T3-L1s were cultured individually (control, CON), with 24-h culture media from each cell type added to the other cell type (replacement, RP) in 2-layer co-culture dishes for 24 h (transwell, TW). M-1s were then exposed to calcium oxalate monohydrate (COM) crystals, and attached (14)C-labeled COM crystals were quantified. Expression of kidney stone- and adipocyte-related genes was analyzed. The radioactivity of adherent COM crystals significantly increased in TW and was relatively higher in RP compared to CON. M-1s demonstrated significant upregulation of adiponectin (Adipoq) in RP and secreted phosphoprotein 1 (Spp1) in TW compared to CON before COM crystal exposure, and significant downregulation of Spp1 in TW and upregulation of tumor necrosis factor (Tnf), interleukin 6 (Il-6), and chemokine (C-C motif) ligand 2 (Ccl2) compared to CON after COM crystal exposure. 3T3-L1s showed significant upregulation of Spp1, Adipoq, Tnf-α, and Ccl2 compared to CON. Enzyme-linked immunosorbent assays of co-culture medium revealed significantly increased TNF-α in TW. Our results highlight the potential for paracrine interactions between renal tubular cells and adipocytes and suggest that MetS conditions may lead to kidney stone formation.

Primary testicular carcinoid tumours (TCT) are very rare, and a large tumour size and the presence of carcinoid syndrome predict a malignant course. Histologically, it is difficult to differentiate between benign and malignant TCTs. We report a case of a primary pure TCT with an unusual presentation in a 23- year-old man, who had an asymptomatic, enlarged scrotum on the right side for 7 years. On gross examination, the tumour was 9.6 cm in diameter. The Ki-67 labelling index was 19.8%. High inguinal orchidectomy was performed, and 30 months after surgery the patient remains asymptomatic.

Mice have a strong ability to eliminate renal calcium oxalate crystals, and our previous examination indicated a susceptibility in which monocyte-macrophage interaction could participate in the phenomenon. To clarify the macrophage-related factors playing roles in the prevention of crystal formation in mouse kidneys, morphologic and expression studies based on microarray pathway analysis were performed. Eight-week-old male C57BL/6N mice were administered 80 mg/kg of glyoxylate by daily intraabdominal injection for 15 days, and the kidneys were extracted every 3 days for DNA microarray analysis. Based on the raw data of microarray analysis, pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokine (C-X-C) ligand 1, fibronectin 1, and major histocompatability (MHC) class II. Association analysis of related gene expression values by quantitative reverse transcription polymerase chain reaction (RT-PCR) indicated the high association of chemokine (C-C) ligand 2, CD44, colony-stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1, and transforming growth factor β1 (TGF-β1) with the amount of both renal crystals and F4/80, a macrophage marker. Immunohistochemically, interstitial macrophages increased during the experimental course, and CD44 and MHC class II were upregulated around crystal-formation sites. Ultrastructural observation of renal macrophages by transmission electron microscopy indicated interstitial macrophage migration with the phagocytosis of crystals. In conclusion, increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte-macrophage migration and phagocytosis via the interaction of CD44 with osteopontin and fibronectin. Such crystal-removing ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation.

Objectives: To clarify the role of renal tubular cell (RTC) injury and oxidative stress in the early stage of renal calcium oxalate crystal formation in a mouse model. Methods: Daily intra-abdominal injections of glyoxylate (1.35 mmol/kg/day) into 8-week-old mice were carried out over 6 days. Kidneys were extracted before and at 6, 12 and 24 h and 3 and 6 days after glyoxylate injection. Crystal formation was detected using Pizzolato staining and polarized light optical microscopy. Immunohistochemical staining and western blotting of superoxide dismutase, and 4-hydroxynonenal and malondialdehyde were carried out in order to observe oxidative stress and lipid peroxidation, respectively. RTC microstructural damage and crystal nuclei formation were observed using transmission electron microscopy. To ameliorate RTC injury, mice were treated with green tea 1 week before and 1 week after glyoxylate administration. The number of crystals and RTC damage were observed and comparisons were made between glyoxylate-treated mice with and without green tea administration. Results: Oxidative stress and lipid peroxidation were observed after 6 h. Crystal nuclei containing collapsed mitochondria and fallen microvilli appeared in the renal distal tubular lumen after 24 h. Crystals occupying the tubular lumen were detected on day 3. The number of crystals in mice receiving green tea was significantly lower than in those receiving glyoxylate alone. Conclusions: RTC injury, especially mitochondrial damage, and oxidative stress induce the early stage of calcium oxalate crystal formation in mice.

Osteopontin (OPN) has been described as playing a nonredundant role in renal crystal formation. Here we investigated the effects of impaired domains of OPN, namely, the Arg-Gly-Asp (RGD) sequence and two calcium-binding sites on crystal formation. We used wild-type mice (WT group), OPN knockout mice (KO group), and OPN knockout mice carrying either a transgene in which the RGD sequence had been modified to Arg-Gly-Glu (RGE group) or whose two calcium-binding sites had been deleted (CaX group). Following intraperitoneal injection of glyoxylate for 9 days, the changes occurring in three parameters of crystal formation—localization, number, and microstructure—were analyzed. In the WT group, crystal deposits increased gradually at the renal corticomedullary junction in an orderly fashion, whereas those in the KO group were observed sporadically in the renal cortex. In both the CaX and RGE groups, deposits were localized near the corticomedullary junction. Crystal deposition was greatest in the WT group and least in the KO group. The number of deposits in the RGE group was nearly equal to that in the KO group. Microscopic observations revealed that the crystal nuclei in the CaX group were stratified and occurred in a disordered pattern; this pattern was dissimilar to that in the WT group, in which a rosette petal–like radial pattern was observed. In the RGE group, the nuclei exhibited a radial pattern similar to that in the WT group. The results indicated the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation. © 2010 American Society for Bone and Mineral Research.

We previously established a mouse kidney stone formation model and showed that mice have a higher tolerance to stone formation than rats. Furthermore, we showed that the generated calcium oxalate crystal deposits could be eliminated after several days. This study investigated the transcriptome of stone formation and elimination in the mouse kidney based on gene selection using a microarray technique. Eight-week-old male C57BL/6N mice were administered 80 mg/kg glyoxylate for 15 days, and kidney calcium oxalate crystal depositions had increased by day 6; thereafter, depositions decreased gradually and had almost disappeared by day 15. On microarray analysis, mRNA expression in the crystal-formed kidneys showed the significant expression of 18,064 genes. Thirty-one, 21, and 25 genes showed at least a 2-fold increased expression during the experimental course (days 3-15), stone formation phase-specific (days 3-6), and stone elimination phase-specific (days 9-15) stages, respectively. Among these genes, those related to chemotaxis and monocyte/macrophage activation were identified. Gene ontology analysis to identify overexpressed genes highlighted categories related to inflammation, immune reactions and the complement activation pathway. Quantitative PCR of 17 previously reported stone-related genes with a significant expression on microarray analysis showed significantly increased chemokines, stone matrix proteins, and their receptors; the significant decrease of several types of transporters and superoxide dismutase; and the persistently high expression of Tamm-Horsfall protein throughout the experiment. In conclusion, inflammation and immune reactivity through macrophage migration are involved in stone formation and elimination in mouse kidneys.

This study was performed to characterize the α1-adrenoceptor subtypes in mouse ureters as regards gene expressions and contractile functions.The mRNAs for these subtypes were quantified by the real-time quantitative reverse transcription polymerase chain reaction. In a functional study, α1-adrenoceptor antagonists were evaluated against the noradrenaline-induced contraction in mouse isolated ureteral preparations.In mouse ureter, the relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 74.5, 14.3 and 11.2%, respectively. Adrenaline and noradrenaline each produced a concentration-dependent phasic contraction (pD 2 values, 5.73±0.05 and 5.69±0.06, respectively). Prazosin (non-selective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist), and BMY-7378 (selective α1D-adrenoceptor antagonist) all shifted the concentration–response curve for noradrenaline to the right, the rank order of potencies (apparent pA 2 values) being silodosin (9.32±0.11)prazosin (8.55±0.10)BMY-7378 (6.06±0.15). The α1A-adrenoceptor antagonist silodosin was thus much more effective than the α1D-adrenoceptor antagonist BYM-7378.Our results demonstrate that in mouse ureters: the mRNA for the α1A-adrenoceptor was more prevalent than those for the α1B- and α1D-adrenoceptors, and that among these subtypes, the α1A-adrenoceptor plays the major role in noradrenaline-induced contraction.

Objective: Osteoporosis is associated with the pathogenesis and risk of urolithiasis, which is higher among postmenopausal women (as opposed to premenopausal). Bisphosphonates potently inhibit bone resorption, and are used in the management of bone disease. We investigated the ability of a bisphosphonate to prevent calcium stone formation. Methods: We studied 12 postmenopausal women (63.8 ± 7.3 years) who were not receiving osteoporosis therapy, and had stones comprised of calcium phosphate (CaP; n = 3), calcium oxalate (CaOx; n = 3) and CaP + CaOx (n = 6). We measured bone mineral density (BMD), serum and urinary values in 24-hour urine specimens before and 3 months after the oral administration of 5 mg/day of alendronate (ALN). The indexes of the ionic activity product of calcium oxalate, AP(CaOx), and of calcium phosphate, AP(CaP), were estimated using the Tiselius method. Results: ALN significantly reduced the AP(CaP) index (1.53 ± 1.37 to 0.89 ± 0.81, p Conclusion: The results suggested that ALN not only improves BMD and osteoporosis, but also reduces the risk of calcium phosphate stone formation in postmenopausal women.

To confirm an inverse relationship between obesity and serum prostate-specific antigen (PSA) levels in Japanese men with a smaller body mass index (BMI) than white and African-American men.We analyzed 5246 apparently healthy Japanese men aged20 years who visited our medical center for a health checkup from January 2004 to December 2006. The men were divided into 6 groups by age decade, and the BMI was categorized into 5 groups. The body fat percentage (BFP) was also used and was grouped into quartiles. The Mantel-Haenszel chi(2) test was used to check for trends in proportions of subjects with abnormal PSA values for each cutoff point (2.5 and 4.0 ng/mL) in these groups. The relationships between the PSA levels and BMI or BFP were examined using multivariate analysis.The median age, BMI, BFP, and PSA level was 46 years, 23.2 kg/m(2), 21.5%, and 0.78 ng/mL, respectively. The proportion of subjects with an abnormal PSA value increased significantly with age (P for trend.0001); however, no trends were found across the BMI or BFP categories. The geometric mean PSA level increased significantly with age (P for linear trend.0001) and decreased with BMI and BFP categories (P for linear trend = .001 and P for linear trend = .002, respectively).Our findings have demonstrated an inverse relationship between obesity and PSA levels even in Japanese men with a low prevalence of obesity, such as was previously reported for American men. Therefore, in prostate cancer screening, obesity, which can affect the accuracy of PSA testing, independent of race and ethnicity, should be taken into account.

Objectives: The transcription factor nuclear factor–κB (NF–κB) is involved in inflammatory and immune responses through the induction of various cytokines and growth factors. Recently, the coordinated action of NF–κB and activator protein-1 was reported in osteopontin (OPN) expression. In the present study, we demonstrated that oxalate induces OPN expression by activating NF–κB in renal tubular cells. Furthermore, we investigated the inhibitory effect of N-acetyl-L-cysteine (NAC) on NF–κB activation in the human renal tubular cell line. Methods: All of the experiments were carried out using human kidney-2 cells, which are human proximal tubular epithelial cells immortalized by transduction with the human papillomavirus 16E6/E7 gene. The time-dependent extraction of total protein was performed after the uptake of 0.5 mM oxalate by the cells. The NF–κB activation and OPN expression were examined by western blotting and immunocytochemistry. Results: As a result of oxalate stimulation, the amount of p65 subunit in the nucleus increased significantly (P

Objectives: To clarify the influence of long-term bed rest on renal stone formation and to analyze the mechanism of bed-rest-induced stone formation and prevention by bisphosphonate and bed-rest exercise. Methods: Twenty-five men aged 26–48 years and divided into control (CON: n = 9), exercise (EX: n = 9), and pamidronate (PMD: n = 7) groups, rested on a 6° head-down tilt bed for 90 days. The exercise group carried out resistive exercise every 3 days. Pamidronate (60 mg) was intravenously given 2 weeks before the initiation of bed rest. Abdominal X-ray examination and urine biochemistry were carried out during 90 days of bed rest and 90 days of reloading. Results: Renal stone formation was observed in two (22.2%) and four (44.4%) subjects in the control and exercise groups, respectively. No stone was seen in the pamidronate group. In the exercise group, urinary oxalate and phosphate excretion were significantly higher than in the control group. In the pamidronate group, urinary calcium excretion and relative supersaturation of calcium oxalate and brushite were lower than in the control group throughout the bed-rest and recovery period. Conclusion: Long-term bed-rest-induced renal stone formation was found to be induced by increased urinary calcium and subsequent crystal formation of calcium oxalate and calcium phosphate. Exercise during bed rest for the prevention of bone mineral loss and contracture might increase the risk of renal stone formation. Pamidronate is useful for the prevention of renal stone formation during and after bed rest.

An important process in kidney stone formation is the conversion of retentive crystals in renal tubules to concrete stones. Osteopontin (OPN) is the major component of the kidney calcium-containing stone matrix. In this study, we estimated OPN function in early morphological changes of calcium oxalate crystals using OPN knockout mice: 100 mg/kg glyoxylate was intra-abdominally injected into wildtype mice (WT) and OPN knockout mice (KO) for a week, and 24-h urine oxalate excretion showed no significant difference between WT and KO. Kidney crystal depositions were clearly detected by Pizzolato staining but not by von Kossa staining in both genotypes, and the number of crystals in KO was significantly fewer than in WT. Morphological observation by polarized light optical microphotography and scanning electron microphotography (SEM) showed large flower-shaped crystals growing in renal tubules in WT and small and uniform crystals in KO. X-ray diffraction detected the crystal components as calcium oxalate monohydrate in both genotypes. Immunohistochemical staining of OPN showed that the WT crystals contained OPN protein but not KO crystals. We concluded that OPN plays a crucial role in the morphological conversion of calcium oxalate crystals to stones in mouse kidneys.

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Objectives: In this decade, there have emerged many alternatives for the therapy of localized prostate cancer, such as brachytherapy, intensity modulated radiation therapy, high intensity focused ultrasound, and retropubic radical prostatectomy. In this retrospective study, we reviewed cases of complications related to laparoscopic radical prostatectomy (LRP) from our institution only, and we evaluated whether this procedure was minimally invasive or not. Methods: Between August 2000 and December 2006, a total of 160 patients in our institution underwent LRP as the definitive treatment for clinically localized prostate cancer. We analyzed not only the complications but also the operative time and blood loss to clarify the indications of LRP. Results: Major complications were defined as those requiring surgical intervention including laparoscopic repair. A total of nine major complications (5.63%) occurred in six patients (3.75%). In a Cox regression analysis, the estimated blood loss (P = 0.0069) and neoadjuvant hormonal therapy (P = 0.0019) were significant predictors of long operative time (>6 h) of LRP. Conclusion: The indication of LRP in this study was localized prostate cancer at the T1 or T2 stage for which neoadjuvant hormonal therapy had not been administered. We concluded that the operative and postoperative morbidities of LRP are low and that LRP can be routinely carried out by an experienced team.

Laparoscopic partial nephrectomy for small renal tumors has been performed with increasing frequency over the past few years. We prospectively evaluated preoperative and postoperative differential renal function in patients with functioning contralateral kidneys who underwent laparoscopic partial nephrectomy using a microwave tissue coagulator without hilar clamping. Seven patients (five men and two women) in this prospective protocol underwent laparoscopic partial nephrectomy for exophytic tumors using a microwave tissue coagulator when the tumor was 2 cm or less in diameter. Renal scanning with 99technetium-labeled diethylenetetraminepentaacetic-acid scan was performed preoperatively and postoperatively at 7 days and 6 months after surgery in all patients. The mean tumor size and surgical duration were 17.0 +/- 2.3 mm and 161.1 +/- 20.5 min, respectively. Intraoperative blood loss was 35.6 +/- 40.7 ml. The preoperative glomerular filtration rate (GFR) and differential split renal function (SF) in the affected kidney were 45.7 +/- 12.8 ml/min and 50.5 +/- 3.3%, respectively. On postoperative day 7 and at 6 months, GFR and SF in the affected kidney were 36.2 +/- 9.0 and 36.8 +/- 10.9 ml/min and 44.3 +/- 4.1 and 45.0 +/- 5.1%, respectively. No postoperative complications occurred. Laparoscopic nonischemic partial nephrectomy using a microwave tissue coagulator has the advantage of technical ease and adequate hemostasis. However, its indication should be restricted to small exophytic renal tumors due to the expected collateral damage causing renal impairment.

Aim: Urinary stone disease is a common condition affecting up to 12% of the population. Speedy elimination of ureterolithiasis in the lower part of ureters is reported with the alpha 1-blocker. This study was carried out to characterize the alpha 1 adrenoceptors (AR) subtype gene and protein expression in the proximal, medial, and distal regions of the human ureter with the aim of facilitating stone expulsion. Methods: The study was carried out on 20 volunteers. Proximal, medial and distal ureter specimens were obtained as discarded tissues after nephroureterectomy for renal pelvic or ureteral carcinoma. Proximal ureter specimens were obtained as discarded tissues after nephrectomy for renal carcinoma. Using ureter samples, real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed. Results: The alpha 1d subtype mRNA was highly expressed in each ureteral region, accounting for about 54% of the total AR Messenger Ribonucleic Acid. In the proximal and medial ureter, the distribution of ARs was alpha 1d ≥ €alpha 1a > alpha 1b as well as that of the total ureter. The distal ureter expressed the highest amount of alpha 1d ARs. The alpha 1d subtype expression tended to be high compared with the alpha 1a subtype expression. In the distal ureter, the distribution of ARs was alpha 1d > alpha 1a > alpha 1b. Immunohistochemical staining revealed that expressions of alpha 1a-AR and alpha 1d-AR were higher than that of alpha 1b-AR. Conclusions: According to our results, we should try the alpha 1d AR antagonist for the conservative expulsive therapy of distal ureteral stones in the highest region of alpha 1d subtype distribution.

Matrix Gla protein, a potent calcification inhibitor in arterial vessels, is also expressed in the kidney and is up-regulated following the administration of ethylene glycol, a precursor of oxalate. Considering the analogous characteristics between arterial calcification and kidney stones, we identified variants of the human matrix Gla protein gene and investigated whether there is an association between MGP genetic polymorphisms and kidney stones.We studied single nucleotide polymorphisms in matrix Gla protein in 122 kidney stone cases and 125 controls. We resequenced the human genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons and 3'-untranslated regions, and we performed systematic genetic analysis. A single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease assay and its association with kidney stones was analyzed.We observed 19 polymorphisms. A single nucleotide polymorphism was associated with kidney stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold decreased kidney stone risk compared with A allele carriers in single nucleotide polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association between the polymorphism and kidney stone clinical characteristics.Our findings show that an MGP gene polymorphism is associated with kidney stones and influences genetic susceptibility to kidney stones. In the future functional assays of the polymorphism should permit better understanding of the role of matrix Gla protein genetic variants and kidney stones.

the predominant component (>60%) of their stone. Patients with

The incidence of urolithiasis has increased in the industrialized nations. However, both the pathogenesis and methods for its prevention remain to be clarified. We demonstrate that the antioxidative effect of green tea decreases the formation of calcium oxalate stones, OPN (osteopontin) expression, and apoptosis, and increases SOD (superoxide dismutase) activity in rat kidney tissues. The inhibitory effect of green tea on calcium oxalate urolithiasis is most likely due to its antioxidative effects. Therefore, we examined oxidative stress in vivo applied to Madin-Darby canine kidney (MDCK) cells, to which catechin, an antioxidant, was added. To evaluate the effects of oxidative stress on MDCK cells, we use a hypoxic condition because hypoxia is known to lead to oxidative stress. Confluent cultures of MDCK cells were exposed to (-)epigallocatechin 3 gallate (EGCG) (0, 0.1, 0.5, 5.0 mg/ml) for 2, 4, 8 or 16 h to determine changes in protein secretion and apoptosis. OPN protein expression was observed in MDCK cells of all 16 groups. The levels of expression of OPN protein were the same among all groups. In all groups, SOD protein expression was observed. In the groups exposed to EGCG 0.5, 5.0 mg/ml, SOD staining was more enhanced than in the EGCG 0 and 0.1 mg/ml groups. No deposits were detected in any of the 16 groups. RT-PCR was performed to detect sequences from OPN (979 bp) and SOD (447 bp). Quantitative analyses showed that SOD activity decreased gradually in all groups. Only in the EGCG 0 mg/ml 16 h group were TUNEL-positive cells observed. In the other groups, TUNEL-positive cells were not detected. EGCG used as an antioxidant protects renal tubular cell from cellular injury caused by oxidative stress through SOD protein expression.

Background: At present, immunotherapeutic agents such as bacillus Calmette-Guerin (BCG) and anti-tumor chemotherapeutic agents in saline are used intravesically in patients with bladder carci- noma. However, of greater significance is the possibility that the saline vehicle may itself promote carcinoma development in the bladder. Methods: The potential promoting effects of intravesical instillation of saline were assessed in female F344 rats. The animals were divided into 3 groups, all of which received 0.05% N-butyl-N- (4-hydroxybutyl)nitrosamine (BBN) in their drinking water for the first 10 weeks. They were then maintained without further treatment (group 1) or received intravesical instillations of 0.3 mL of saline or distilled water once a week for 6 weeks, 15 weeks after the end of the BBN treatment (groups 2 and 3). At 32 weeks, all the animals were killed and examined immunohistochemically with proliferating cell nuclear antigen (PCNA) antibody, as well as by routine histopathologic examination. Results: Both the incidence and the number of bladder carcinomas were higher in the animals that received instillations of saline than in those who did not receive the instillations. Significant increases in tumor size were also noted for the saline-treated groups, although this was not linked with the PCNA labeling index. Conclusions: The results indicate that saline is a promoter of urinary bladder carcinogenesis either because of the catheterization or the fluid itself.

Purpose: To evaluate the efficacy of endoscopic combined intrarenal surgery (ECIRS) using retrograde flexible ureteroscopy and miniature percutaneous nephrolithotomy (PNL) for the treatment of patients with staghorn calculi in the prone split-leg position.We retrospectively reviewed the records of 42 patients with staghorn calculi (45.8±3.2 mm) who underwent ECIRS using retrograde flexible ureteroscopy and miniature PNL in the prone split-leg position for the treatment of staghorn calculi in our center between December 2010 and August 2013. A flexible ureteroscope with a laser fiber was inserted through a ureteral access sheath, and lithoclast lithotripsy was performed through a mini-percutaneous tract. Both procedures were performed simultaneously by two urologists. Surgical parameters, including surgical time, stone-free (SF) rates, modified Clavien complication grades, and risk factors for residual stones, were analyzed.Fifteen patients (35.7%) had complete staghorn calculi. Among the 42 staghorn calculi treated, 23 had 0 to 5 stone branches, 14 had 6 to 10 stone branches, and 5 had ≥11 stone branches. All procedures were performed successfully using a single lithotripsy tract with the patient in the prone split-leg position. The mean surgical time was 143.2±9.2 minutes. The initial SF rate was 71.4%, and the final SF rate was 83.3% after further treatment. One patient required a blood transfusion (2.4%), but no patient experienced a ≥3 Clavien grade complication. Risk factors for residual stones were stone size, stone surface area, complete staghorn calculi, and the number of stone branches.ECIRS for staghorn calculi in the prone split-leg position is a safe, efficient, and versatile method for the effective management of staghorn calculi without the creation of multiple percutaneous tracts.

We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation.Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively.The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells.Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types.

We report our experience of laparoscopic nephrectomy on a girl with giant hydronephrosis of a horseshoe kidney. An 8-year-old girl presented with a 4-month history of right abdominal pain. We performed laparoscopic nephrectomy for the non-functioning moiety of a horseshoe kidney secondary to uretero-pelvic junction obstruction. Laparoscopic nephrectomy is a feasible and safe method with good indications especially for children with a horseshoe kidney disease.

To examine the relationship between urolithiasis and calcification of the aortic artery.We examined the relationship between urolithiasis and calcification of the aortic artery in 181 patients with urinary calcium stones (stone group) and in 181 without a history of urolithiasis (control group). All patients underwent abdominal CT to score the degree of calcification at the aortic arterial wall, as follows: 0, none; 1,120 degrees calcification; 2,or =120 degrees to240 degrees calcification; and 3,or =240 degrees calcification. Both the stone and control groups were further classified into three groups each according to gender and age.Aortic calcification scores differed significantly between the stone and control groups in males agedor =20-40 years (0.43+/-0.50 vs 0.13+/-0.35, respectively) and in females agedor =60 years (1.81+/-0.74 vs 1.44+/-0.64, respectively).These findings suggest that common causative factors are associated with urolithiasis and arteriosclerosis and that adult males with arteriosclerosis develop urolithiasis more easily than those without.

Purpose The purpose of this study was to evaluate the efficacy of retroperitoneal laparoscopic ureterolithotomy for the management of large proximal ureteric stones and the impact of this treatment on postoperative renal function. Methods The data of 12 patients (7 men and 5 women; mean age, 68.5 ± 8.9 years) with large pyeloureteral junction (2 cases) and upper ureteral (10 cases) stones (25.3 ± 7.4 mm) that had undergone retroperitoneal laparoscopic ureterolithotomy were reviewed. Renal function was analyzed by the estimated glomerular filtration rate (eGFR) and renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) before and 3 months after surgery. Results The mean operative time was 129.5 ± 21.4 minutes, with a mean blood loss of 64.4 ± 78.2 mL. The mean duration of hospital stay after surgery was 6.4 ± 2.7 days, and the mean duration of stenting was 7.2 ± 1.7 weeks. A stone clearance rate of 100% was achieved, and no patient developed ureteric stricture. 99mTc-MAG3 scintigraphy showed that laparoscopic removal of calculi did not affect renal function, but did improve ureteral occlusion. Conclusions Retroperitoneal laparoscopic ureterolithotomy is a safe and effective treatment option for reducing ureteral obstruction in select patients with large proximal ureteric stones.

Background Residents (n = 157) of Kamisu City, Ibaraki, Japan, were orally exposed to diphenylarsinic acid (DPAA) via the ingestion of contaminated underground water. Subsequently, a clinical syndrome associated with a variety of cerebellar and brainstem symptoms, was observed in 20 of the 30 residents who consumed high concentrations of DPAA in the contaminated well water. While the clinical symptoms of DPAA were defined, the toxicokinetics of DPAA remained unclear. Methods In order to investigate the underlying toxicokinetics of DPAA, we collected serum and cerebrospinal fluid (CSF) samples from 5 patients with DPAA intoxication, and attempted to estimate the half-life of serum DPAA and the CSF/serum ratio of DPAA. Results DPAA, and its derivatives, such as phenylmethylarsinic acid (PMAA) and phenylarsinic acid (PAA), were detected in serum from residents exposed to DPAA. Serum DPAA was observed for > 200 days after the last ingestion of contaminated water. The half-life of serum DPAA was 22.5 days in children and 39.4 days in youths and adults, which was nearly double that observed in children. DPAA was found in CSF, and the CSF/serum ratios of DPAA in 2 patients were 3.0% and 3.7%, respectively, suggesting that this toxicant is able to cross the blood–brain barrier. Conclusion An established animal model of DPAA intoxication was examined regarding the toxicokinetics, distribution and direct DPAA accumulation in the cerebrum. On the basis of existing animal data, and the present results arising from human subjects, the development of new therapies for DPAA intoxication should be enhanced, such as accelerated DPAA excretion.

after every 250 shocks. Stone comminution was assessed with X-ray KUB after 1 month and 3 months. Renal injures were assessed with 24 hours urinary microalbumin and beta 2 microglobulin levels pre-procedure, immediately post procedure and 7 days after procedure. Standard statistical methods were used for data analysis. RESULTS: Among the patients, M: F ratio was 2:1. Mean age was 38 years. Stone size ranges from 7 ? 15 mm. In escalating voltage group, 75% were stone free where in fixed voltage group, 72 % were stone free. There was significant difference between urinary microalbumin and beta 2 microglobulin levels both immediately post procedure and 7 days after procedure which were statistically significant. CONCLUSIONS: Although there is no significant difference in stone comminution between the fixed and escalating voltage strategies, renal injuries are significantly less in escalating voltage strategy compared to fixed voltage strategy.

Clinical managements of chronic pain in rheumatoid arthritis (RA) and osteoarthritis (OA) require deep understanding of patients. Since medication is mostly set under the guidelines of RA and OA to control of pain, but personal characteristics is not so much paid attention in terms of preferences. In the present study, alcohol preference was analyzed in the patients prescribed pregabalin and tramadol/acetaminophen in our hospital. All consecutive patients were requested to write up the medical questionnaire sheet before medical examination. The responses to this sheet are completely subjective. The close relation between habitual alcohol drinking and adherence of analgesics was observed in terms of adherence of pregabalin and tramadol/acetaminophen. That is, in OA patients, alcohol drinkers showed good adherence to pregabalin and also tramadol/acetaminophen. However, in RA patients, alcohol drinkers showed higher ratio to good adherence, but there was no significance between alcohol drinkers and non-alcohol drinkers. When total patients were analyzed, alcohol drinkers showed significantly higher adherence with pregabalin and also tramadol/acetaminophen. Therefore, it is recommended that precise personal preference had better to be taken in medical examination before prescription of pregabalin and tramadol/ acetaminophen in RA and OA patients.

Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.

treated mice had stones. The number of stones ranged from 16-45 (25.86 / 10.96, n 181). All stones were in the small group, except one 3mm stone. Mean stone weight was 29.2 / 14.8mg (range 14.2-52.3mg). Mean bladder weight in mice with stones was 65.4 / 18.6mg (range 42.2-101.1) and without stones it was 18.6 / 5.2mg (range 10.2-25.2mg). Stone number, stone weight, and bladder weight were significantly different between the two groups (two-tailed t-test, p 0.05) and the difference in stone burden between the groups was clearly evident by micro CT. There was no significant difference in cystine concentration (nmol/mg creatinine) between the two groups (5,410 / 2,124 versus 4,343 / 1,577), suggesting that urine was saturated with cystine in both groups. CDME treatment had no side effects. A dose of 5 mg/ml administered in the water supply also had beneficial effects and no side effects. CONCLUSIONS: CDME-treated mice had a significantly smaller stone mass and stone size, strongly suggesting that CDME is inhibiting, but not preventing, the growth of cystine crystals into stones. While current treatments for cystinuria in humans have poor compliance and multiple side effects, CDME in mice had therapeutic potential and was without adverse effects. Further research is warranted to determine if CDME may provide a new treatment approach for cystinuria, which is clinically invaluable, since cystinuria patients are at risk for multiple surgeries and renal insufficiency.

by renal macrophages was observed under a transmitted electron microscope (TEM). RESULTS: Experiment 1: J774.1 indicated higher COM crystal phagocytosis rate than M1 (p 0.0038). The rate increased along with the increase in exposure to the COM crystals (COM, 12.5 g/cm: 19.3 5.86%; COM, 62.5 g/cm: 39.7 5.51%). The phagocytosis rates in the CB groups were significantly lower than those in the non-CB groups (COM, 12.5 g/cm: 0.7 1.15%, p 0.0056; COM, 62.5 g/cm: 13.3 3.21%, p 0.0020). Experiment 2: The number of renal tubular crystals increased until day 6 and thereafter decreased and disappeared until day 15. Renal macrophages appeared in the interstitium, and their number increased or decreased, correlating with the amount of crystals. The TEM image demonstrated phagocytosis of the crystals by interstitial macrophages. CONCLUSIONS: Macrophages have the ability to englobe calcium oxalate crystals and thus play an active role in preventing kidney stone formation.

In 2002, speedy elimination of ureterolithiasis in the lower part of ureter was first reported with the alpha 1 blocker. Thereafter, there are a lot of reports including meta-analysis about tamsulosin. In 2011 EAU Guidelines on Urolithiasis, it is the most important to establish effective MET (medical expulsive therapy) to facilitate spontaneous stone passage. Alpha 1 blockers are the preferred agents for MET. As a basic evidence for MET, we reported that alpha 1a and 1d AR subtype mRNA was highly expressed in the human ureter and that alpha 1A AR is the main participant in the human ureteral contraction. It is published newly in Japanese Guidelines on Urolithiasis revised edition to schedule to be published soon.